title: Mutation survey of known LCA genes and loci in the Saudi Arabian population.
abstract: OBJECTIVE
  The purpose of this study was to perform a comprehensive survey of all known Leber congenital amaurosis (LCA) genes and loci in a collection of 37 consanguineous LCA families from Saudi Arabia.
  
  
  METHODS
  Direct PCR and sequencing were used to screen 13 known LCA genes (GUCY2D, CRX, RPE65, TULP1, AIPL1, CRB1, RPGRIP1, LRAT, RDH12, IMPDH1, CEP290, RD3, LCA5). In addition, families without mutations identified were further screened with STR markers around these 13 known LCA genes and two loci.
  
  
  RESULTS
  Disease-causing mutations were identified in nine of the 37 families: five in TULP1, two in CRB1, one in RPE65, and one in GUCY2D. Mutations in known genes only accounted for 24% of the Saudi families--much less than what has been observed in the European population (65%). Phenotype-genotype analysis was carried out to investigate the LCA disease penetrance for all families whose mutations identified. All identified mutations were found to segregate perfectly with the disease phenotype. On the other hand, severity of the disease varies for different patients carrying the same mutation and even within the same family. Furthermore, based on homozygosity mapping with both STR and SNP markers, one family is likely to map to the LCA3 locus.
  
  
  CONCLUSIONS
  These results underscore the importance of studying LCA disease families from different ethnic backgrounds to identify additional novel LCA disease genes. Furthermore, perfect segregation between mutation and disease indicates that LCA is fully penetrant. However, phenotypic variations among patients carrying the same mutation suggest that at least some of the variations in the clinical phenotype is due to modification from the genetic background, environment, or other factors.
authors.affiliation: Departments of Molecular and Human Genetics.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jianlan
authors.initials: J
authors.lastname: Peng
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Richard Alan
authors.initials: RA
authors.lastname: Lewis
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Graeme
authors.initials: G
authors.lastname: Mardon
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D001766:Blindness / Q000208:ethnology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005796:Genes; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics; D012162:Retinal Degeneration / Q000208:ethnology / Q000235:genetics*; D012529:Saudi Arabia / Q000208:ethnology; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C448939:CRB1 protein, human; C105443:TULP1 protein, human; C110715:guanylate cyclase 1